Abstract SNACC-34

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Does Genetic Susceptibility to Persistent Post-op Pain (Thermal Hyperalgesia) Correlate with Other Phenotypes in the Mouse Phenome Database (MPD)?

1Fu E, 2Boucekkine H, 1Wishnek S, 1Martin E, 1Levitt R
1University of Miami, Pembroke Pines, FL, USA; 2Univeristy of Miami, Pembroke Pines, FL, USA

Background: We hypothesized that genetic susceptibility to maladaptive responses following nerve injury is due to common pathways that affect pain and neuropsychiatric responses (i.e., anxiety). In this study, we measured thermal hyperalgesia after nerve injury in 16 inbred mouse strains, by calculating the Persistent Pain Index (PPI). We calculated heritability and compared our PPI neurobehavior phenotype with datasets from other laboratories that measured pain and anxiety phenotypes in multiple inbred strains in the Jackson Laboratories Mouse Phenome Database (MPD).
Methods: Chronic construction injury (CCI) of sciatic nerve was used as a model of persistent post-operative pain. Briefly, the left sciatic nerve was exposed and 3 loose 6.0 silk ligatures were loosely placed around the dissected nerve. Baseline nociception and post-CCI thermal hyperalgesia were tested in each animal using a mobile infrared heat lamp device, positioned underneath the targeted hind paw. Baseline measurements were obtained two days prior to CCI surgery. Behavioral tests were performed at Baseline, Days 1, 7, 14 and 21 after CCI. The PPI was calculated as the area under the curve based on cumulative thermal measurements (Hargreaves) over 21 days. Strains of inbred mice with greater PPI are demonstrating less thermal hyperalgesia, as measured by minimal change in their withdrawal latency over time. Using the MPD, we compared our thermal PPI data with pain phenotype data from Mogil et al., (Pain 2002;97:75-86) and anxiety phenotype data from O’Leary et al.. (Behav Genet 2013;43:34-50), using Pearson coefficients.
Results: The PPI response of 16 inbred strains of mice is shown in Figure 1. Heritability estimates based on 16 strains for thermal hypersensitivity at Baseline and for PPI are presented in Table 1. We found a thermal PPI heritability of 75% and the calculation of effective factors on the order of 2.73 estimates the number of independently segregating genes with equivalent phenotypic effects that can account for the observed strain differences. Comparison with two datasets in the MPD showed that there was statistically significant Pearson coefficients for the following: 1) head dipping anxiety behavior (r=0.8560, P=0.0017), 2) thermal hyperalgesia after carrageenan hindpaw inflammation (r=0.814, P=0.023), and 3) von Frey neurosensory mechanical withdrawal (r=0.877, P=0.049).
Discussion: The thermal PPI is heritable and preliminary analysis indicates that thermal PPI after nerve injury correlates with several neurobehavior phenotypes in the MPD. These data suggest that common pathways of genetic susceptibility may explain cognitive and neurosensory behaviors.

  • SNACC-34 Image 2
  • SNACC-34 Image 1

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